The Physiology of Pregnancy, Parturition and Lactation M. Djauhari Widjajakusumah Fakultas Kedokteran Universitas Indonesia The Physiology of Pregnancy, Parturition and Lactation M. Djauhari Widjajakusumah Fakultas Kedokteran Universitas Indonesia

PregnancyPregnancy

CLEAVAGE AND IMPLANTATION

human Chorionic Gonadotropin (hCG) Produced by syncytiotrophoblast Produced by syncytiotrophoblast hCG-α is identical to α subunit LH, FSH and TSH hCG-α is identical to α subunit LH, FSH and TSH Is primarily luteinizing and luteotropic, little FSH activity Is primarily luteinizing and luteotropic, little FSH activity Detected in the urine as early as 14 days after conception Detected in the urine as early as 14 days after conception Acts on the same receptor as LH Acts on the same receptor as LH Produced by syncytiotrophoblast Produced by syncytiotrophoblast hCG-α is identical to α subunit LH, FSH and TSH hCG-α is identical to α subunit LH, FSH and TSH Is primarily luteinizing and luteotropic, little FSH activity Is primarily luteinizing and luteotropic, little FSH activity Detected in the urine as early as 14 days after conception Detected in the urine as early as 14 days after conception Acts on the same receptor as LH Acts on the same receptor as LH

Other Placental Hormones human Chorionic Somatomammotropin (hCS) human Chorionic Somatomammotropin (hCS)  Produced by syncytiotrophoblast  Large amount of human placental lactogen / hPL (lactogenic activity)  Small amount of chorionic growth hormone-prolactin /CGP (growth-stimulating activity) olarge quantities in maternal blood, very little reaches the fetus ofunctions as “maternal growth hormone of pregnancy” ohCS levels are proportionate to the size of placenta  low hCS levels are sign of placental insufficiency human Chorionic Somatomammotropin (hCS) human Chorionic Somatomammotropin (hCS)  Produced by syncytiotrophoblast  Large amount of human placental lactogen / hPL (lactogenic activity)  Small amount of chorionic growth hormone-prolactin /CGP (growth-stimulating activity) olarge quantities in maternal blood, very little reaches the fetus ofunctions as “maternal growth hormone of pregnancy” ohCS levels are proportionate to the size of placenta  low hCS levels are sign of placental insufficiency

Other Placental Hormones Relaxin Relaxin  Produced by placenta, uterus, corpus luteum, mammary glands, prostate gland  Relaxes the pubic symphysis, pelvic joints  Softens and dilates the uterine cervix  facilitates delivery Relaxin Relaxin  Produced by placenta, uterus, corpus luteum, mammary glands, prostate gland  Relaxes the pubic symphysis, pelvic joints  Softens and dilates the uterine cervix  facilitates delivery

Hormone levels in human maternal blood during normal pregnancy Hormone Time of Peak Secretion hCGFirst trimester RelaxinFirst trimester hCSTerm Estradiol Term Estriol Term Progesterone Term Prolactin Term Hormone Time of Peak Secretion hCGFirst trimester RelaxinFirst trimester hCSTerm Estradiol Term Estriol Term Progesterone Term Prolactin Term

ParturitionParturition

ParturitionParturition Estrogens increase the number of oxytocin receptors in myometrium > 100 x during pregnancy Estrogens increase the number of oxytocin receptors in myometrium > 100 x during pregnancy Reaches its peak during early labor Reaches its peak during early labor Uterine distention late in pregnancy may also increase the number of oxytocin receptors Uterine distention late in pregnancy may also increase the number of oxytocin receptors Increased number of oxytocin receptors causes uterus to respond to normal plasma oxytocin concentration in the early labor stage Increased number of oxytocin receptors causes uterus to respond to normal plasma oxytocin concentration in the early labor stage Estrogens increase the number of oxytocin receptors in myometrium > 100 x during pregnancy Estrogens increase the number of oxytocin receptors in myometrium > 100 x during pregnancy Reaches its peak during early labor Reaches its peak during early labor Uterine distention late in pregnancy may also increase the number of oxytocin receptors Uterine distention late in pregnancy may also increase the number of oxytocin receptors Increased number of oxytocin receptors causes uterus to respond to normal plasma oxytocin concentration in the early labor stage Increased number of oxytocin receptors causes uterus to respond to normal plasma oxytocin concentration in the early labor stage

ParturitionParturition Estrogens  Increased oxytocin receptors  Uterine distention Prostaglandin Prostaglandin Uterine contractions Dilatation of cervix and distention of vagina Stimuli from cervix and vagina Increased secretion of oxytocin Estrogens  Increased oxytocin receptors  Uterine distention Prostaglandin Prostaglandin Uterine contractions Dilatation of cervix and distention of vagina Stimuli from cervix and vagina Increased secretion of oxytocin

Parturition Parturition Oxytocin increases unterine contractions in two ways: 1.Acts directly on myometrium, uterine smooth muscles contract 2.Stimulates prostaglandins formation in the decidua. Prostaglandins enhance the oxytocin-induced contractions Spinal reflexes and voluntary contractions of abdominal muscles also aid in delivery Oxytocin increases unterine contractions in two ways: 1.Acts directly on myometrium, uterine smooth muscles contract 2.Stimulates prostaglandins formation in the decidua. Prostaglandins enhance the oxytocin-induced contractions Spinal reflexes and voluntary contractions of abdominal muscles also aid in delivery

STAGES OF LABOR

Mammary Gland and Lactation

Development of The Breasts Estrogens are primarily responsible for proliferation of mammary ducts Estrogens are primarily responsible for proliferation of mammary ducts Progesterone are primarily responsible for the development of the lobules Progesterone are primarily responsible for the development of the lobules Prolactin in humans may also be needed for mammary glands development at puberty Prolactin in humans may also be needed for mammary glands development at puberty Increased prolactin levels, and high levels of estrogens and progesterone (and possibly hCG) cause full breast lobulo-alveolar development during pregnancy Increased prolactin levels, and high levels of estrogens and progesterone (and possibly hCG) cause full breast lobulo-alveolar development during pregnancy Cortisol, insulin, and growth hormone are necessary for mammary development Cortisol, insulin, and growth hormone are necessary for mammary development Estrogens are primarily responsible for proliferation of mammary ducts Estrogens are primarily responsible for proliferation of mammary ducts Progesterone are primarily responsible for the development of the lobules Progesterone are primarily responsible for the development of the lobules Prolactin in humans may also be needed for mammary glands development at puberty Prolactin in humans may also be needed for mammary glands development at puberty Increased prolactin levels, and high levels of estrogens and progesterone (and possibly hCG) cause full breast lobulo-alveolar development during pregnancy Increased prolactin levels, and high levels of estrogens and progesterone (and possibly hCG) cause full breast lobulo-alveolar development during pregnancy Cortisol, insulin, and growth hormone are necessary for mammary development Cortisol, insulin, and growth hormone are necessary for mammary development

MAMMARY GLAND

Lactation – Secretion and Ejection of Milk Prolactin causes formation and secretion of milk in estrogen- and progesterone-primed breasts Prolactin causes formation and secretion of milk in estrogen- and progesterone-primed breasts Oxytocin causes contraction of myoepithelial cells, leads to milk ejection through the nipple Oxytocin causes contraction of myoepithelial cells, leads to milk ejection through the nipple Estrogens increase the number of oxytocin receptors on myoepithelial cells Estrogens increase the number of oxytocin receptors on myoepithelial cells Estrogens (and possibly also progesterone) antagonize the milk production effect of prolactin Estrogens (and possibly also progesterone) antagonize the milk production effect of prolactin After parturition, abrupt decline of estrogens and progesterone initiates lactation – in humans takes 1-3 days for the milk to “come in” After parturition, abrupt decline of estrogens and progesterone initiates lactation – in humans takes 1-3 days for the milk to “come in” Prolactin causes formation and secretion of milk in estrogen- and progesterone-primed breasts Prolactin causes formation and secretion of milk in estrogen- and progesterone-primed breasts Oxytocin causes contraction of myoepithelial cells, leads to milk ejection through the nipple Oxytocin causes contraction of myoepithelial cells, leads to milk ejection through the nipple Estrogens increase the number of oxytocin receptors on myoepithelial cells Estrogens increase the number of oxytocin receptors on myoepithelial cells Estrogens (and possibly also progesterone) antagonize the milk production effect of prolactin Estrogens (and possibly also progesterone) antagonize the milk production effect of prolactin After parturition, abrupt decline of estrogens and progesterone initiates lactation – in humans takes 1-3 days for the milk to “come in” After parturition, abrupt decline of estrogens and progesterone initiates lactation – in humans takes 1-3 days for the milk to “come in”

Prolactin – Synthesis and Control Produced by the lactotrophs cells of the anterior pituitary gland Produced by the lactotrophs cells of the anterior pituitary gland Under stimulatory control of thyroid releasing hormone (TRH) Under stimulatory control of thyroid releasing hormone (TRH) Increased release at night Increased release at night In females - increased release during puberty In females - increased release during puberty Prolactin levels are high during pregnancy - oestrogen causes an increase in numbers of lactotrophs Prolactin levels are high during pregnancy - oestrogen causes an increase in numbers of lactotrophs During lactation, suckling of the breast results in an increased release of prolactin ( decreased PIH, increased PRH) During lactation, suckling of the breast results in an increased release of prolactin ( decreased PIH, increased PRH) Response to suckling declines with time post-partum, may well remain above normal for 18 months or more if suckling frequency is maintained at a high level basal levels Response to suckling declines with time post-partum, may well remain above normal for 18 months or more if suckling frequency is maintained at a high level basal levels Produced by the lactotrophs cells of the anterior pituitary gland Produced by the lactotrophs cells of the anterior pituitary gland Under stimulatory control of thyroid releasing hormone (TRH) Under stimulatory control of thyroid releasing hormone (TRH) Increased release at night Increased release at night In females - increased release during puberty In females - increased release during puberty Prolactin levels are high during pregnancy - oestrogen causes an increase in numbers of lactotrophs Prolactin levels are high during pregnancy - oestrogen causes an increase in numbers of lactotrophs During lactation, suckling of the breast results in an increased release of prolactin ( decreased PIH, increased PRH) During lactation, suckling of the breast results in an increased release of prolactin ( decreased PIH, increased PRH) Response to suckling declines with time post-partum, may well remain above normal for 18 months or more if suckling frequency is maintained at a high level basal levels Response to suckling declines with time post-partum, may well remain above normal for 18 months or more if suckling frequency is maintained at a high level basal levels

Prolactin Levels High during pregnancy, drifts down to its normal level after the baby is born High during pregnancy, drifts down to its normal level after the baby is born By the end of the first week after birth, prolactin is down to 50 percent of its normal level, after three or four months, it is the same as it was before pregnancy By the end of the first week after birth, prolactin is down to 50 percent of its normal level, after three or four months, it is the same as it was before pregnancy Every time the baby suckles, there is a new burst of prolactin telling the body to make milk and a burst of oxytocin telling it to eject the milk Every time the baby suckles, there is a new burst of prolactin telling the body to make milk and a burst of oxytocin telling it to eject the milk The more the mother nurses the baby, the more milk the body will produce; suckling is simply the message to the body to make more of it. The more the mother nurses the baby, the more milk the body will produce; suckling is simply the message to the body to make more of it. High during pregnancy, drifts down to its normal level after the baby is born High during pregnancy, drifts down to its normal level after the baby is born By the end of the first week after birth, prolactin is down to 50 percent of its normal level, after three or four months, it is the same as it was before pregnancy By the end of the first week after birth, prolactin is down to 50 percent of its normal level, after three or four months, it is the same as it was before pregnancy Every time the baby suckles, there is a new burst of prolactin telling the body to make milk and a burst of oxytocin telling it to eject the milk Every time the baby suckles, there is a new burst of prolactin telling the body to make milk and a burst of oxytocin telling it to eject the milk The more the mother nurses the baby, the more milk the body will produce; suckling is simply the message to the body to make more of it. The more the mother nurses the baby, the more milk the body will produce; suckling is simply the message to the body to make more of it.

Contraceptive effect of high levels of prolactin In non breast-feeding women  FSH levels quickly return to normal menstrual cycle levels within a week or two post-partum; having the 1 st menstrual period + 6 weeks after delivery In non breast-feeding women  FSH levels quickly return to normal menstrual cycle levels within a week or two post-partum; having the 1 st menstrual period + 6 weeks after delivery

Contraceptive effect of high levels of prolactin In breast-feeding women In breast-feeding women  During lactational amenorrhoea (25-30 weeks) FSH levels appear to be inadequate for ovarian function  LH levels are very low immediately postpartum, by 15 to 20 days increase significantly and remain throughout lactation on the lower side of normal  Prolactin inhibits normal pulsatile secretion of GnRH, inhibits GnRH action on pituitary, antagonize gonadotropin action on ovaries, no midcycle LH surge  anovulation  Prolactin inhibits the ovary  estrogen deficient In breast-feeding women In breast-feeding women  During lactational amenorrhoea (25-30 weeks) FSH levels appear to be inadequate for ovarian function  LH levels are very low immediately postpartum, by 15 to 20 days increase significantly and remain throughout lactation on the lower side of normal  Prolactin inhibits normal pulsatile secretion of GnRH, inhibits GnRH action on pituitary, antagonize gonadotropin action on ovaries, no midcycle LH surge  anovulation  Prolactin inhibits the ovary  estrogen deficient

Newborn Baby Body-weight Loss Newborns are nourished from their mother's milk or from a bottle because they can only swallow liquids. Newborns are nourished from their mother's milk or from a bottle because they can only swallow liquids. Since newborns can only digest about 30 milliliters of mother's milk or formula at a time, they must be fed often, usually about every 4 hours. Since newborns can only digest about 30 milliliters of mother's milk or formula at a time, they must be fed often, usually about every 4 hours. They can lose as much as 10% of their body weights in the first few days after birth because they need more food than they can consume. At about the tenth day of life, the newborn regains the lost weight and starts to gain about 28 grams per day. They can lose as much as 10% of their body weights in the first few days after birth because they need more food than they can consume. At about the tenth day of life, the newborn regains the lost weight and starts to gain about 28 grams per day. Newborns are nourished from their mother's milk or from a bottle because they can only swallow liquids. Newborns are nourished from their mother's milk or from a bottle because they can only swallow liquids. Since newborns can only digest about 30 milliliters of mother's milk or formula at a time, they must be fed often, usually about every 4 hours. Since newborns can only digest about 30 milliliters of mother's milk or formula at a time, they must be fed often, usually about every 4 hours. They can lose as much as 10% of their body weights in the first few days after birth because they need more food than they can consume. At about the tenth day of life, the newborn regains the lost weight and starts to gain about 28 grams per day. They can lose as much as 10% of their body weights in the first few days after birth because they need more food than they can consume. At about the tenth day of life, the newborn regains the lost weight and starts to gain about 28 grams per day.

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